11-72019260-C-T

Position:

• chr11-72019260-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006185.4(NUMA1):​c.584+234G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 152,240 control chromosomes in the GnomAD database, including 64,144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.92 (64144 hom., cov: 31)
• Consequence: NUMA1 NM_006185.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.941

Genes affected

NUMA1 (HGNC:8059): (nuclear mitotic apparatus protein 1) This gene encodes a large protein that forms a structural component of the nuclear matrix. The encoded protein interacts with microtubules and plays a role in the formation and organization of the mitotic spindle during cell division. Chromosomal translocation of this gene with the RARA (retinoic acid receptor, alpha) gene on chromosome 17 have been detected in patients with acute promyelocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ENSG00000251143 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUMA1	NM_006185.4	c.584+234G>A		intron_variant		ENST00000393695.8	NP_006176.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUMA1	ENST00000393695.8	c.584+234G>A		intron_variant		1	NM_006185.4	ENSP00000377298.4

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139317 AN: 152122 Hom.: 64111 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.939

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.916 AC: 139407 AN: 152240 Hom.: 64144 Cov.: 31 AF XY: 0.912 AC XY: 67879 AN XY: 74448

Gnomad4 AFR AF: 0.836

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.957

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.940

Alfa AF: 0.951 Hom.: 29784

Bravo AF: 0.908

Asia WGS AF: 0.870 AC: 3024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.92
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs949326; hg19: chr11-71730306;